Intraperitoneal dissemination of Ad12-induced undifferentiated neuroectodermal hamster tumors: de novo methylation and transcription patterns of integrated viral and of cellular genes

Hohlweg, U.; Hösel, Marianna; Dorn, Andreas; Webb, Dennis; Hilger‐Eversheim, Kristina; Remus, Ralph; Schmitz, Birgit; Buettner, Reinhold; Schramme, Anja; Corzilius, Lars; Niemann, A; Doerfler, Walter

doi:10.1016/j.virusres.2003.08.012

Cited by 21 publications

(32 citation statements)

References 40 publications

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“…In accordance with our finding that E1A-12 functions to activate neuronal gene expression, intraperitoneal and subcutaneous tumors induced by Ad12 in rodents have been shown to contain neuroectodermal characteristics and to express several neuronal genes (29,49,51). Interestingly, it has been found that several other nonneuronal tumors, including breast, ovarian, colorectal, and pancreatic cancers, also display aberrant expression of neuronal genes (2,11,21,23,75).…”

Section: Discussionsupporting

confidence: 89%

Induction of Neuronal and Tumor-Related Genes by Adenovirus Type 12 E1A

Guan

Williams

Ricciardi

2009

J Virol

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Section: Discussionsupporting

confidence: 89%

Induction of Neuronal and Tumor-Related Genes by Adenovirus Type 12 E1A

Guan

Williams

Ricciardi

2009

J Virol

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“…For example, neonatal hamster kidney cells transformed with adenovirus type 12 exhibit a 40% increase in genomic cytosine methylation (Gunthert et al, 1976). While it is thought that this increased DNA methylation may be part of a host defense mechanism attempting to silence expression of foreign DNA (Sutter and Doerfler, 1980), it is also clear that viral infection affects de novo methylation and transcription of cellular genes as well (Heller et al, 1995;Remus et al, 1999;Hohlweg et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Human polyomavirus BKV transcriptionally activates DNA methyltransferase 1 through the pRb/E2F pathway

et al. 2006

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Many DNA tumor virus oncogenes are capable of activating and highjacking the host cell's DNA replication machinery for its own reproduction purposes through targeting and inactivation of the retinoblastoma pocket protein family. Pocket proteins function to regulate cell cycle progression and DNA synthesis through inhibitory interactions with the E2F transcription factors. The interaction of viral oncogenes with the pocket proteins is crucial for their transforming activity. We recently demonstrated that the DNA methyltransferase 1 (DNMT1) gene is an E2F target gene that is transcriptionally activated in cells lacking the retinoblastoma gene (Rb À/À ). Overexpression of DNMT1 is implicated in tumor suppressor gene hypermethylation which is associated with tumorigenesis. Given that viral oncogenes potently stimulate E2F activity, we hypothesized that viral infection might activate DNMT1 and thereby promote transformation. Herein, we demonstrate that DNMT1 is strongly activated by the human polyomavirus BKV large T antigen (TAg) and adenovirus E1a. Viral oncogene mutants incapable of binding the pocket proteins are ineffective at activating DNMT1 compared to their wildtype counterparts. Additionally, mutation of the E2F sites within the DNMT1 promoters dramatically abrogates transcriptional activation. These data suggest that viral induction of DNMT1 through modulation of the pRB/ E2F pathway may be involved in viral transformation.

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“…Another observation of potentially significant concern which has been documented upon Ad12 DNA integration in vitro (6,34) and in vivo (15) and also in some instances following Ad vector integration in cultured cells (43) has been chromosomal deletions, sometimes of substantial size, and rearrangements (12,28,36). We believe that with current technology, this cannot be easily demonstrated in liver tissue.…”

Section: Downloaded Frommentioning

confidence: 82%